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Hormone Replacement Therapy Associated White Blood Cell DNA Methylation and Gene Expression are Associated With Within-Pair Differences of Body Adipo…
2015
The loss of estrogen during menopause causes changes in the female body, with wide-ranging effects on health. Estrogen-containing hormone replacement therapy (HRT) leads to a relief of typical menopausal symptoms, benefits bone and muscle health, and is associated with tissue-specific gene expression profiles. As gene expression is controlled by epigenetic factors (including DNA methylation), many of which are environmentally sensitive, it is plausible that at least part of the HRT-associated gene expression is due to changes in DNA methylation profile. We investigated genome-wide DNA methylation and gene expression patterns of white blood cells (WBCs) and their associations with body compo…
Increase in viral gastroenteritis outbreaks in Europe and epidemic spread of new norovirus variant.
2004
Background Highly publicised outbreaks of norovirus gastroenteritis in hospitals in the UK and Ireland and cruise ships in the USA sparked speculation about whether this reported activity was unusual. Methods We analysed data collected through a collaborative research and surveillance network of viral gastroenteritis in ten European countries (England and Wales were analysed as one region). We compiled data on total number of outbreaks by month, and compared genetic sequences from the isolated viruses. Data were compared with historic data from a systematic retrospective review of surveillance systems and with a central database of viral sequences. Findings Three regions (England and Wales,…
Cohort profile: Thrombolysis in Ischemic Stroke Patients (TRISP): a multicentre research collaboration
2018
PurposeThe ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration aims to address clinically relevant questions about safety and outcomes of intravenous thrombolysis (IVT) and endovascular thrombectomy. The findings can provide observational information on treatment of patients derived from everyday clinical practice.ParticipantsTRISP is an open, investigator-driven collaborative research initiative of European stroke centres with expertise in treatment with revascularisation therapies and maintenance of hospital-based registries. All participating centres made a commitment to prospectively collect data on consecutive patients with stroke treated with IVT using standardised definiti…
Molecular and Translational Classifications of DAMPs in Immunogenic Cell Death
2015
The immunogenicity of malignant cells has recently been acknowledged as a critical determinant of efficacy in cancer therapy. Thus, besides developing direct immunostimulatory regimens, including dendritic cell-based vaccines, checkpoint-blocking therapies, and adoptive T-cell transfer, researchers have started to focus on the overall immunobiology of neoplastic cells. It is now clear that cancer cells can succumb to some anticancer therapies by undergoing a peculiar form of cell death that is characterized by an increased immunogenic potential, owing to the emission of the so-called "damage-associated molecular patterns" (DAMPs). The emission of DAMPs and other immunostimulatory factors by…
Piloting a Smart Rollator : User experiences with technology-related motivation and physical activity
2021
Background: Improved life expectancy combined with suboptimal physical activity (PA)represents an increasingly salient public health challenge among the elderly. PA in late life is associated with fewer health problems in old age. Assistive information and communication technology might improve PA and alleviate health problems among the elderly.Objective: This pilot study aimed to quantitatively measure the motivational aspects relatedto rollator use and, by using qualitative interviews, outline how a Smart Rollator solution would motivate older adults to increase their PA in their everyday lives.Method: A total of 19 subjects between the ages of 63 and 91 years participated in the study. H…
Metalloprotease meprin beta generates nontoxic N-terminal amyloid precursor protein fragments in vivo.
2011
Identification of physiologically relevant substrates is still the most challenging part in protease research for understanding the biological activity of these enzymes. The zinc-dependent metalloprotease meprin β is known to be expressed in many tissues with functions in health and disease. Here, we demonstrate unique interactions between meprin β and the amyloid precursor protein (APP). Although APP is intensively studied as a ubiquitously expressed cell surface protein, which is involved in Alzheimer disease, its precise physiological role and relevance remain elusive. Based on a novel proteomics technique termed terminal amine isotopic labeling of substrates (TAILS), APP was identified …
Clinical implications ofCYP3Apolymorphisms
2006
Due to their enormous substrate spectrum CYP3A4, -3A5 and -3A7 constitute the most important drug-metabolising enzyme subfamily in humans. CYP3As are expressed predominantly, but not exclusively, in the liver and intestine, where they participate in the metabolism of 45 - 60% of currently used drugs and many other compounds such as steroids and carcinogens. CYP3A expression and activity vary interindividually due to a combination of genetic and nongenetic factors such as hormone and health status, and the impact of environmental stimuli. Over the past several years, genetic determinants have been identified for much of the variable expression of CYP3A5 and -3A7, but not for CYP3A4. Using th…
Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells
2013
Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth an…
MYOCARDIAL POTENCY OF AQUEOUS EXTRACT OF HARUNGANA MADAGASCARIENSIS STEM BARK AGAINST ISOPROTERENOL-INDUCED MYOCARDIAL DAMAGE IN RATS
2018
Objectives: The present study was undertaken to evaluate the effects of Harungana madagascariensis on electrocardiographical, biochemical and histopathological changes in isoproterenol (ISO)-induced myocardial infarction in rats. Methods: Male Wistar albino rats were randomly divided and treated with the aqueous extract of Harungana madagascariensis stem bark (AEHM, 200 and 400 mg/kg per os), or normal saline or vitamin E for 7 days with concomitant administration of ISO (85 mg/kg, subcutaneously) on 8th and 9th days, at 24 h interval. Results: The ISO injections to the rats caused cardiac dysfunction evidenced by a marked (P<0.01) elevation in ST-segment, a reduction in R wave amplitude (P…
Feasibility of a personal health technology-based psychological intervention for men with stress and mood problems: Randomized controlled pilot trial
2013
BackgroundWork-related stress is a significant problem for both people and organizations. It may lead to mental illnesses such as anxiety and depression, resulting in increased work absences and disabilities. Scalable interventions to prevent and manage harmful stress can be delivered with the help of technology tools to support self-observations and skills training. ObjectiveThe aim of this study was to assess the feasibility of the P4Well intervention in treatment of stress-related psychological problems. P4Well is a novel intervention which combines modern psychotherapy (the cognitive behavioral therapy and the acceptance and commitment therapy) with personal health technologies to deliv…